Etude de la cyclostationnarité du signal Doppler sanguin pour la détection de micro-emboles : étude préliminaire

Ce papier traite de la détection ultrasonore de micro-emboles par un système Doppler transcrânien. L'originalité de ce travail réside dans le fait que nous utilisons les propriétés cyclostationnaires du signal Doppler ultrasonore sanguin pour détecter des micro-emboles, depuis lors, masqués dans les phases de systoles-diastoles du cycle cardiaque. Dans cette étude nous évaluons théoriquement, à partir d'un modèle réaliste du signal Doppler sanguin, le spectre de corrélation. Nous proposons un paramètre informatif permettant la détection de micro-emboles et nous quantifions les performances du détecteur associé pour le comparer à un détecteur standard

Earlier Detection of Breast Cancer with Ultrasound Molecular Imaging in a Transgenic Mouse Model

Abstract While there is an increasing role of ultrasound for breast cancer screening in patients with dense breast, conventional anatomical ultrasound lacks sensitivity and specificity for early breast cancer detection. In this study, we assessed the potential of ultrasound molecular imaging using clinically translatable vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted microbubbles (MBVEGFR2) to improve the diagnostic accuracy of ultrasound in earlier detection of breast cancer and ductal carcinoma in situ (DCIS) in a transgenic mouse model [FVB/N-Tg(MMTV-PyMT)634Mul]. In vivo binding specificity studies (n = 26 tumors) showed that ultrasound imaging signal was significantly higher (P &amp;lt; 0.001) using MBVEGFR2 than nontargeted microbubbles and imaging signal significantly decreased (P &amp;lt; 0.001) by blocking antibodies. Ultrasound molecular imaging signal significantly increased (P &amp;lt; 0.001) when breast tissue (n = 315 glands) progressed from normal [1.65 ± 0.17 arbitrary units (a.u.)] to hyperplasia (4.21 ± 1.16), DCIS (15.95 ± 1.31), and invasive cancer (78.1 ± 6.31) and highly correlated with ex vivo VEGFR2 expression [R2 = 0.84; 95% confidence interval (CI), 0.72–0.91; P &amp;lt; 0.001]. At an imaging signal threshold of 4.6 a.u., ultrasound molecular imaging differentiated benign from malignant entities with a sensitivity of 84% (95% CI, 78–88) and specificity of 89% (95% CI, 81–94). In a prospective screening trail (n = 63 glands), diagnostic performance of detecting DCIS and breast cancer was assessed and two independent readers correctly diagnosed malignant disease in more than 95% of cases and highly agreed between each other [intraclass correlation coefficient (ICC) = 0.98; 95% CI, 97–99]. These results suggest that VEGFR2-targeted ultrasound molecular imaging allows highly accurate detection of DCIS and breast cancer in transgenic mice and may be a promising approach for early breast cancer detection in women. Cancer Res; 73(6); 1689–98. ©2012 AACR.</jats:p

Gadolinium: pharmacokinetics and toxicity in humans and laboratory animals following contrast agent administration

AbstractGadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use.</jats:p

Abstract OT2-01-01: Trial in Progress: Clinical Utility of Fluoroestradiol F18 PET/CT in Metastatic Breast Cancer Patients with ER-Positive and HER2-Negative Primary Lesions after Progression on First Line Hormonal Therapy

Abstract BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy are the recommended first-line standard-of-care (SOC) treatment for estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients. After progression on first-line treatment, current clinical practice guidelines (NCCN, ESMO) recommend to sequence endocrine therapy (in absence of visceral crisis) until there is no clinical benefit after up to 3 regimens, and subsequently initiate chemotherapy regimens. However, clinical benefit for endocrine monotherapy after progression on first-line standard-of-care is limited, with median progression-free survival (PFS) of 2-5 months. Multiple factors can contribute to endocrine therapy resistance, including changes in ER expression, (epi)genetic mutations, and/or clonal selection under therapeutic pressure. ER heterogeneity can occur over time (temporal) as well as between lesions in a patient (spatial). As confirmed by tissue biopsy, greater than 20% of MBC patients have discordance in ER expression between their primary tumor and a metastatic lesion. Measuring total ER heterogeneity in a patient – the variation in ER expression at whole body level across all MBC lesions – is not clinically feasible by tissue biopsy alone. Fluoroestradiol F18 (Cerianna), also called 18F-FES, is a radioactive diagnostic agent that can be used with PET/CT for in vivo detection of ER-positive lesions in MBC with high accuracy. Results from 18F-FES PET/CT studies have shown that ER expression across MBC lesions at whole body level is heterogeneous in approximately half of ER-positive, HER2-negative MBC patients. In this study, we aim to evaluate the clinical utility of 18F-FES PET/CT to guide second-line treatment decision in ER-positive, HER2-negative MBC patients with progressive disease on first-line SOC hormonal therapy. METHODS: Fluoroestradiol F18 (Cerianna) is being evaluated in a phase 4, open-label, prospective cohort study enrolling 206 patients at 20-30 centers in the United States. Patients diagnosed with ER-positive, HER2-negative MBC who have progressive disease on first-line aromatase inhibitor therapy with or without CDK4/6 inhibitor will be included in the study; patients with isolated hepatic metastases will be excluded. All patients will undergo an 18F-FES PET/CT scan. The treating physician will complete a standardized questionnaire to indicate the second-line therapeutic management plan before the scheduled 18F-FES PET/CT. After interpretation of 18F-FES PET/CT by local radiologist or nuclear medicine physician, imaging results will be provided to the treating physician who will then fill out a similar questionnaire to specify the final therapeutic decision. The proportion of patients with a change in therapeutic management plan based on incorporation of 18F-FES PET/CT results will be the primary endpoint. During the study follow-up period of 18 months, data on SOC imaging, treatments/procedures received, and clinical outcomes will be collected. Secondary endpoints include visual and quantitative heterogeneity assessment of tumor 18F-FES uptake, and PFS rates at 6 months and 18 months after 18F-FES PET/CT, which will be assessed between patients with and without a change in therapeutic management plan. The trial is planned to begin enrollment in Q3 2022. Clinical trial information: NCT05068726 Citation Format: Stephanie van de Ven, Feng Luo, Nicholas DiGregorio, Adolfo Fuentes-Alburo, Francois Tranquart. Trial in Progress: Clinical Utility of Fluoroestradiol F18 PET/CT in Metastatic Breast Cancer Patients with ER-Positive and HER2-Negative Primary Lesions after Progression on First Line Hormonal Therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-01.</jats:p